Estradiol-induced prolactinomas: differential effects on dopamine in posterior pituitary and median eminence.
Prolactin release is inhibited by dopamine and stimulated by estradiol. Dopamine is released from nerve terminals in the median eminence and posterior pituitary. Estradiol may act directly on the anterior pituitary or by modulating the two dopaminergic systems. Estradiol treatment induces the formation of prolactinomas in Fischer 334 rats. Therefore, this strain was chosen as the experimental model. The first objective was to determine whether estradiol differentially regulates the two dopaminergic systems. The second objective was to explore whether the anterior pituitary in estradiol-treated rats acquires the capability for de novo synthesis of dopamine. Rats were ovariectomized and implanted with estradiol capsules (OVEX + E2). Controls were untreated ovariectomized rats (OVEX). Three weeks thereafter, rats were killed. Anterior and posterior pituitaries and medial basal hypothalami (MBH) were removed and individually incubated for 60 min in Hank's balanced salt solution containing 10 microCi [3H-]tyrosine. The median eminence was then dissected from the MBH. Tissues were homogenized in perchloric acid and the supernatant fluids were extracted with alumina. Both endogenous and tritiated dopamine were simultaneously quantitated by HPLC. Prolactinoma formation in OVEX + E2 rats was confirmed by dramatic rise (50-fold) in plasma prolactin levels and marked enlargement (3-fold) of the anterior pituitary. Estradiol treatment caused a significant 60% reduction in both dopamine content and synthesis in the median eminence. In contrast, estradiol treatment affected neither dopamine content nor synthesis in the posterior pituitary. There was no evidence for de novo synthesis of dopamine in anterior pituitaries from either OVEX or OVEX + E2 rats. We conclude that the two dopaminergic systems which regulate prolactin secretion, exhibit a differential response to estradiol.
Burgett
R A
RA
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46223.
Garris
P A
PA
Ben-Jonathan
N
N
D000818:Animals; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D004958:Estradiol; D005260:Female; D008473:Median Eminence / Q000378:metabolism*; D009929:Organ Size; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D015175:Prolactinoma / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D004958:Estradiol; D011388:Prolactin; D004298:Dopamine